title: The ZFP-1(AF10)/DOT-1 complex opposes H2B ubiquitination to reduce Pol II transcription.
abstract: The inhibition of transcriptional elongation plays an important role in gene regulation in metazoans, including C. elegans. Here, we combine genomic and biochemical approaches to dissect a role of ZFP-1, the C. elegans AF10 homolog, in transcriptional control. We show that ZFP-1 and its interacting partner DOT-1.1 have a global role in negatively modulating the level of polymerase II (Pol II) transcription on essential widely expressed genes. Moreover, the ZFP-1/DOT-1.1 complex contributes to progressive Pol II pausing on essential genes during development and to rapid Pol II pausing during stress response. The slowing down of Pol II transcription by ZFP-1/DOT-1.1 is associated with an increase in H3K79 methylation and a decrease in H2B monoubiquitination, which promotes transcription. We propose a model wherein the recruitment of ZFP-1/DOT-1.1 and deposition of H3K79 methylation at highly expressed genes initiates a negative feedback mechanism for the modulation of their expression.
authors.affiliation: Department of Biochemistry and Molecular Biophysics, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
authors.forename: Germano
authors.initials: G
authors.lastname: Cecere
authors.forename: Sebastian
authors.initials: S
authors.lastname: Hoersch
authors.forename: Morten B
authors.initials: MB
authors.lastname: Jensen
authors.forename: Shiv
authors.initials: S
authors.lastname: Dixit
authors.forename: Alla
authors.initials: A
authors.lastname: Grishok
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D004257:DNA Polymerase II / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D017238:Genes, Helminth; D018869:Heat-Shock Response; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D021381:Protein Transport; D034622:RNA Interference; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D054875:Ubiquitination
chemical_list: D029742:Caenorhabditis elegans Proteins; D006657:Histones; D014157:Transcription Factors; C579560:Zfp-1 protein, C elegans; C583336:DOT-1.1 protein, C elegans; D011495:Histone-Lysine N-Methyltransferase; D004257:DNA Polymerase II